The specific aims of this research proposal are (a) to determine whether the protein kinase closely associated with RNA polymerase I (Rose, Stetler, Jacob, Proc. Natl. Acad. Sci. U.S., in press) is structurally related (peptide mapping) to the free protein kinase, purified to homogeneity in our laboratory (Rose, Bell, Siefken, Jacob, J. Biol. Chem., in press), (b) to investigate whether the protein kinase from the tumor is distinct from the corresponding liver enzyme in structure, catalytic activity and specificity in RNA polymerase I phosphorylation, (c) to investigate the exact role of the protein kinase in cloned rDNA transcription, (d) to study the effect of protein kinase on RNA polymerase I activity and rRNA synthesis in vivo, following microinjection into viable cells where rRNA synthesis is at reduced level, (e) to produce hybridomas producing monoclonal antibodies against the protein kinase and microinject the antibodies into viable cells to see whether the rRNA synthesis is preferentially blocked, (f) to establish whether the increase in rRNA synthesis in liver observed after administration of glucocorticoid (to adrenelectomized rats), carcinogens (24 hr after treatment) and complete amino acid mixture or tryptophan alone (to starved rats), is due to enhanced protein kinase activity associated with RNA polymerase I, (g) to investigate whether the augmented protein kinase activity is due to increased amount of the enzyme and whether it is related to the amount of translatable mRNA for the kinase, and (h) to determine whether this protein kinase is involved in cell growth in view of the fact that rRNA synthesis is a hall mark of almost all growing cells. If the antibodies against the protein kinase can indeed inhibit the stimulatory level of rRNA synthesis, it is plausible to envisage the preferential killing of cancer cells using these antibodies. If protein kinase from the tumor is structurally and antigenically distinct from the liver enzyme, the production of monoclonal antibodies against the tumor enzyme might be further useful in the selective arrest of tumor cells.